The objective of the proposed research is to develop the inbred germfree (GF) rat and mouse fed chemically defined (CD) diet (with low molecular weight, water-soluble, ultrafiltered components) as the most completely defined animal model for immunology, nutrition, physiology, pharmacology and oncology. Such a model must be not only defined in its environmental parameters, but also defined (characterized) in its own morphologic and functional parameters as they may affect future experimental use. Reproducing colonies of GF-CD C3H mice have been obtained and are being immunologically characterized. Further adjustment of CD diet formulations is being carried out to eliminate a residuum of perinatal mortality in GF-CD mice otherwise normal in growth and lifespan. Dietary supplements and substitutions to alter nutrient content and physicochemical character of the CD diet will be tested and refined for this purpose. Characterization of both GF-diet and GF-CD-diet rats and mice will be continued to evaluate the effects on the animal of GF status and of CD diet, especially to study mechanisms in areas where notable differences from conventional animals have been found. These include differences in cecal size and contents, intestinal transit, nutrient absorption, mucosal epithelial renewal, cholesterol-bile acid metabolism, minimum oxygen consumption, energy balance, and thyroid maturation and decline. Immunological effects of the GF-CD environment will be evaluated in terms of circulating immune globulins, response to mitogens and to injection of sheep red blood cells, macrophage further dietary improvement in the present colony, for cholesterol-bile acid studies related to cardiovascular disease and colon cancer.